Abstract
Immune checkpoints (ICs) have pivotal roles in regulating immune responses. The inhibitory ICs in the tumor microenvironment (TME) have been implicated in the immune evasion of tumoral cells. Therefore, identifying and targeting these inhibitory ICs might be critical for eliminating tumoral cells. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory IC that is expressed on myeloid cells, lymphoid cells, and tumoral cells; therefore, VISTA can substantially regulate innate and adaptive anti-tumoral immune responses. Besides, growing evidence indicates that VISTA blockade can enhance the sensitivity of tumoral cells to conventional IC-based immunotherapy, e.g., cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. In this regard, the current study aimed to review the current evidence about the structure and expression pattern of VISTA, its role in TME, the clinicopathological significance of VISTA, and its prognostic values in various cancers. Besides, this review intended to collect the lessons from the recent pre-clinical and clinical studies and propose a strategy to overcome tumor immune-resistance states.
Highlights
Growing evidence indicates that inhibitory/stimulatory Immune checkpoints (ICs) have critical roles in regulating immune responses [1]
These findings suggest that dual blockade of V-domain immunoglobulin suppressor of T cell activation (VISTA) and programmed death receptor 1 (PD-1) can have a synergistic effect on regulating T cells
Since VISTA expression on tumor cells can lead to tumor development and it signaling pathway is different from the signaling pathways of other inhibitory ICs such as programmed cell death ligand 1 (PD-L1), dual blockade of tumoral VISTA/PD-L1 can lead to the synergic inhibitory effect on tumor development [41]
Summary
Growing evidence indicates that inhibitory/stimulatory ICs have critical roles in regulating immune responses [1] These IC axes can be established between tumor-infiltrating immune cells and tumoral cells, which have led to the development of novel immunotherapy approaches [2, 3]. VISTA in Cancer Therapy from anti-tumoral immune responses Suppressing these inhibitory ICs has gained special attention in treating various cancers [4,5,6]. Targeting these inhibitory ICs, e.g., CTLA4 and programmed death receptor 1 (PD-1), has been associated with activated anti-tumoral immune responses in affected patients [7,8,9]. The review intended to highlight the role of VISTA in regulating immune responses and immune-resistant states following conventional IC-based immunotherapy in various cancers
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